|
1
|
Bedenić B, Martinko K, Đermić E, Vujić L, Ivanković S, Miloš M, Feliciello I, Đermić D. Antibacterial Effect of Phenylboronic Acid on Escherichia coli and Its Potential Role as a Decontaminant of Fresh Tomato Fruits. Food Technol Biotechnol 2025; 63:66-73. [PMID: 40322280 PMCID: PMC12044292 DOI: 10.17113/ftb.63.01.25.8771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 02/13/2025] [Indexed: 05/08/2025] Open
Abstract
Research background Food safety is threatened by the contamination of fresh fruits and vegetables by pathogenic bacteria, among which the particularly widespread ones are coliform bacteria. Due to the continuous increase in the incidence of severe diseases caused by the consumption of fresh (tomato) fruits contaminated with Escherichia coli, antimicrobial postharvest measures are needed. The problem is that many active antimicrobial compounds have a weak and short-lasting effect and/or are not environmentally friendly. Recently, the antibacterial and antifungal activity of environmentally friendly agent phenylboronic acid (PBA), including on two tomato pathogens, has been reported. Experimental approach The aim of this study is to determine the antibacterial effect of PBA on E. coli and three enteropathogenic Enterobacterales, and to check its ability to serve as a bacterial decontaminant of fresh tomato fruits. Results and conclusions The minimum inhibitory concentration (MIC) of PBA against E. coli, as well as Shigella sonnei, Salmonella enteritidis and Yersinia enterocolitica was 1.0, 1.2, 1.0 and 0.8 mg/mL, respectively. In addition, we have shown that PBA has a bacteriostatic effect on E. coli at lower concentrations and a bactericidal effect at higher (>3.0 mg/mL) concentrations. Importantly, the study found that an E. coli strain resistant to seven commonly used antibiotics, as well as strains producing extended-spectrum beta-lactamases (ESBL), is as sensitive to PBA as the wild-type strain without any resistance, suggesting that the mechanism of action of PBA differs from that of all these antibiotics. Finally, we have shown that washing and incubating contaminated tomato fruits in PBA solution reduces the growth of E. coli washed from fresh tomato fruits in a concentration- (0.5-3.0 mg/mL) and time-dependent manner, while having no adverse effect on the tomato fruits. Novelty and scientific contribution This is the first report on the antibacterial effect of PBA on medically important bacteria E. coli, S. enteritidis, S. sonnei and Y. enterocolitica. Moreover, we show that PBA kills multidrug-resistant E. coli, including those producing ESBL, making it a promising agent against such bacteria. Finally, PBA is shown to be an effective decontaminant of E. coli on fresh tomato fruits.
Collapse
Affiliation(s)
- Branka Bedenić
- Biomedical Research Center Šalata-BIMIS University of Zagreb School of Medicine, Department for Clinical Microbiology and Infection prevention and Control, University Hospital Centre Zagreb, Croatia
| | - Katarina Martinko
- University of Zagreb Faculty of Agriculture, Division of Phytomedicine, Department of Plant Pathology, Zagreb, Croatia
| | - Edyta Đermić
- University of Zagreb Faculty of Agriculture, Division of Phytomedicine, Department of Plant Pathology, Zagreb, Croatia
| | - Lovorka Vujić
- University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Siniša Ivanković
- Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia
| | - Mladen Miloš
- Faculty of Chemistry and Technology, University of Split, Split, Croatia
| | - Isidoro Feliciello
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy
| | - Damir Đermić
- Ruđer Bošković Institute, Division of Molecular Biology, Zagreb, Croatia
| |
Collapse
|
|
2
|
Rezk MM. A comparative neuro-study of solo or accompanied low and high boric acid doses with date molasses in adult male albino rats. Environ Anal Health Toxicol 2024; 39:e2024026-0. [PMID: 39973072 PMCID: PMC11852289 DOI: 10.5620/eaht.2024026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 10/11/2024] [Indexed: 01/03/2025] Open
Abstract
Boric acid (BA) is a weak acid and the simplest compound resulting from the dissolution of boron in water. There is great competition to determine whether boron is an essential or nonessential nutrient. Date molasses is a potent type of sweetener with valuable components, such as flavonoids and phenolics, and has significant health benefits. This study investigated the neuro-essentiality and neurotoxicity of boric acid boron in adult male albino rat cortex and cerebellum brain areas and the impact of date molasses treatment. Animals were grouped into the following groups: control, low and high boric acid doses, 10 and 500 mg/kg, respectively, with or without 250 mg/kg date molasses. The results revealed the ability of BAs to cross the blood-brain barrier and accumulate in the cerebellum and cortex, revealing the ability of date molasses to decrease BA accumulation at different time intervals. Additionally, the results varied between a nonsignificant increase or decrease in calcium ion content, monoamines (norepinephrine, dopamine, and serotonin), glucose, adenosine triphosphate, malondialdehyde and glutathione, depending on the BA dose. Moreover, date molasses mitigated any unwanted BA results. In conclusion, boric acid, which is within a permissible limit, could be essential and have a neuroprotective effect, whereas at a sublethal level, it could have a neurotoxic effect. Additionally, Date molasses can have neuroprotective effects and antagonize the neurotoxic effects of boric acid through its antioxidant and scavenging effects.
Collapse
Affiliation(s)
- Mohamed M. Rezk
- Isotopes Department, Research sector, Nuclear Materials Authority, Cairo, Egypt
| |
Collapse
|
|
3
|
Resina L, Esteves T, Pérez-Rafael S, García JIH, Ferreira FC, Tzanov T, Bonardd S, Díaz DD, Pérez-Madrigal MM, Alemán C. Dual electro-/pH-responsive nanoparticle/hydrogel system for controlled delivery of anticancer peptide. BIOMATERIALS ADVANCES 2024; 162:213925. [PMID: 38908101 DOI: 10.1016/j.bioadv.2024.213925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 05/24/2024] [Accepted: 06/09/2024] [Indexed: 06/24/2024]
Abstract
An electro-chemo-responsive carrier has been engineered for the controlled release of a highly hydrophilic anticancer peptide, CR(NMe)EKA (Cys-Arg- N-methyl-Glu-Lys-Ala). Remotely controlled on demand release of CR(NMe)EKA, loaded in electro-responsive poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles, has been achieved by applying electrical stimuli consisting of constant positive (+0.50 V) or negative voltages (-0.50 V) at pre-defined time intervals. In addition, after loading CR(NMe)EKA/PEDOT nanoparticles into an injectable pH responsive hydrogel formed by phenylboronic acid grafted to chitosan (PBA-CS), the efficiency of the controlled peptide release has increased approximately by a factor of 2.6. The hydration ratio of such hydrogel is significantly lower in acidic environments than in neutral and basic media, which has been attributed to the dissociation of the boronate bonds between polymer chains. Hence, the electro-controlled peptide release from PBA-CS/CR(NMe)EKA/PEDOT hydrogels, in the acidic environment of tumors, combines the effects of the oxidation and reduction of PEDOT chains on the interactions with the peptide and the carrier, with the peptide concentration gradient at the interface between the collapsed hydrogel and the release medium. Furthermore, the peptide released by electro-stimulation preserved its bioactivity assessed by promoting human prostate cancer cells death. Overall, this work is a promising attempt to develop a carrier platform for small hydrophilic anticancer peptides, which delivery rationale is synergistically regulated by the electrical and pH responsiveness of the carrier.
Collapse
Affiliation(s)
- Leonor Resina
- Departament d'Enginyeria Química and Barcelona Research Center for Multiscale Science and Engineering, EEBE, Universitat Politècnica de Catalunya, C/ Eduard Maristany 10-14, 08019 Barcelona, Spain; iBB - Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico - Universidade de Lisboa, Avenida Rovisco Pais 1, 1049-001 Lisboa, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais 1, 1049-001 Lisboa, Portugal
| | - Teresa Esteves
- iBB - Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico - Universidade de Lisboa, Avenida Rovisco Pais 1, 1049-001 Lisboa, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais 1, 1049-001 Lisboa, Portugal
| | - Sílvia Pérez-Rafael
- Grup de Biotecnologia Molecular i Industrial, Department of Chemical Engineering, Universitat Politècnica de Catalunya, Rambla Sant Nebridi 22, Terrassa 08222, Spain
| | - José Ignacio Hernández García
- Departmento de Química Orgánica, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 3, La Laguna 38206, Tenerife, Spain; Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 2, La Laguna 38206, Tenerife, Spain
| | - Frederico Castelo Ferreira
- iBB - Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico - Universidade de Lisboa, Avenida Rovisco Pais 1, 1049-001 Lisboa, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais 1, 1049-001 Lisboa, Portugal
| | - Tzanko Tzanov
- Grup de Biotecnologia Molecular i Industrial, Department of Chemical Engineering, Universitat Politècnica de Catalunya, Rambla Sant Nebridi 22, Terrassa 08222, Spain
| | - Sebastian Bonardd
- Departmento de Química Orgánica, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 3, La Laguna 38206, Tenerife, Spain; Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 2, La Laguna 38206, Tenerife, Spain
| | - David Díaz Díaz
- Departmento de Química Orgánica, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 3, La Laguna 38206, Tenerife, Spain; Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 2, La Laguna 38206, Tenerife, Spain.
| | - Maria M Pérez-Madrigal
- Departament d'Enginyeria Química and Barcelona Research Center for Multiscale Science and Engineering, EEBE, Universitat Politècnica de Catalunya, C/ Eduard Maristany 10-14, 08019 Barcelona, Spain.
| | - Carlos Alemán
- Departament d'Enginyeria Química and Barcelona Research Center for Multiscale Science and Engineering, EEBE, Universitat Politècnica de Catalunya, C/ Eduard Maristany 10-14, 08019 Barcelona, Spain; Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
| |
Collapse
|
|
4
|
Paşa S, Atlan M, Temel H, Türkmenoğlu B, Ertaş A, Okan A, Yilmaz S, Ateş Ş. Histopathological, Antioxidant, and Enzyme Activity of Boronic Incorporated Catechin Compound: Screening of Bioactivity with Molecular Docking Studies. RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY 2024; 50:1446-1465. [DOI: 10.1134/s1068162024040216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 12/13/2023] [Accepted: 12/14/2023] [Indexed: 01/03/2025]
|
|
5
|
Cordova-Chávez RI, Trujillo-Ferrara JG, Padilla-Martínez II, González-Espinosa H, Abad-García A, Farfán-García ED, Ortega-Camarillo C, Contreras-Ramos A, Soriano-Ursúa MA. One-Step Synthesis, Crystallography, and Acute Toxicity of Two Boron-Carbohydrate Adducts That Induce Sedation in Mice. Pharmaceuticals (Basel) 2024; 17:781. [PMID: 38931447 PMCID: PMC11206247 DOI: 10.3390/ph17060781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 06/08/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
Boronic acids form diester bonds with cis-hydroxyl groups in carbohydrates. The formation of these adducts could impair the physical and chemical properties of precursors, even their biological activity. Two carbohydrate derivatives from d-fructose and d-arabinose and phenylboronic acid were synthesized in a straightforward one-step procedure and chemically characterized via spectroscopy and X-ray diffraction crystallography. Additionally, an acute toxicity test was performed to determine their lethal dose 50 (LD50) values by using Lorke's method. Analytical chemistry assays confirmed the formation of adducts by the generation of diester bonds with the β-d-pyranose of carbohydrates, including signals corresponding to the formation of new bonds, such as the stretching of B-O bonds. NMR spectra yielded information about the stereoselectivity in the synthesis reaction: Just one signal was found in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests showed that the LD50 value for both compounds was 1265 mg/kg, while the effective dose 50 (ED50) for sedation was 531 mg/kg. However, differences were found in the onset and lapse of sedation. For example, the arabinose derivative induced sedation for more than 48 h at 600 mg/kg, while the fructose derivative induced sedation for less than 6 h at the same dose without the death of the mice. Thus, we report for the first time two boron-containing carbohydrate derivatives inducing sedation after intraperitoneal administration. They are bioactive and highly safe agents. Further biological evaluation is desirable to explore their medical applications.
Collapse
Affiliation(s)
- Ricardo Ivan Cordova-Chávez
- Laboratorio de Neurofisiología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Mexico City 11340, Mexico; (R.I.C.-C.); (H.G.-E.); (A.A.-G.)
- Laboratorio de Bioquímica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Mexico City 11340, Mexico;
| | - José G. Trujillo-Ferrara
- Laboratorio de Bioquímica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Mexico City 11340, Mexico;
| | - Itzia I. Padilla-Martínez
- Laboratorio de Química Supramolecular y Nanociencias, Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Av. Acueducto s/n, Barrio la Laguna Ticomán, Mexico City 07340, Mexico;
| | - Héctor González-Espinosa
- Laboratorio de Neurofisiología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Mexico City 11340, Mexico; (R.I.C.-C.); (H.G.-E.); (A.A.-G.)
| | - Antonio Abad-García
- Laboratorio de Neurofisiología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Mexico City 11340, Mexico; (R.I.C.-C.); (H.G.-E.); (A.A.-G.)
| | - Eunice D. Farfán-García
- Laboratorio de Bioquímica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Mexico City 11340, Mexico;
| | - Clara Ortega-Camarillo
- Medical Research Unit in Biochemistry, Specialties Hospital, National Medical Center SXXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Alc. Cuauhtémoc, Mexico City 06720, Mexico;
| | - Alejandra Contreras-Ramos
- Laboratory of Molecular Biology in the Congenital Malformations Unit, Children’s Hospital of Mexico Federico Gomez (HIMFG), Calle Dr. Marques 162, Col. Doctores, Alc. Cuahutémoc, Mexico City 06720, Mexico;
| | - Marvin A. Soriano-Ursúa
- Laboratorio de Neurofisiología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Mexico City 11340, Mexico; (R.I.C.-C.); (H.G.-E.); (A.A.-G.)
| |
Collapse
|
|
6
|
Shirani E, Razmjou A, Asadnia M, Nordon RE, Inglis DW. Surface Modification of Polystyrene with Boronic Acid for Immunoaffinity-Based Cell Enrichment. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2024; 40:4361-4372. [PMID: 38357828 DOI: 10.1021/acs.langmuir.3c03644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/16/2024]
Abstract
Obtaining an enriched and phenotypically pure cell population from heterogeneous cell mixtures is important for diagnostics and biosensing. Existing techniques such as fluorescent-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) require preincubation with antibodies (Ab) and specialized equipment. Cell immunopanning removes the need for preincubation and can be done with no specialized equipment. The majority of the available antibody-mediated analyte capture techniques require a modification to the Abs for binding. In this work, no antibody modification is used because we take advantage of the carbohydrate chain in the Fc region of Ab. We use boronic acid as a cross-linker to bind the Ab to a modified surface. The process allows for functional orientation and cleavable binding of the Ab. In this study, we created an immunoaffinity matrix on polystyrene (PS), an inexpensive and ubiquitous plastic. We observed a 37% increase in Ab binding compared with that of a passive adsorption approach. The method also displayed a more consistent antibody binding with 17 times less variation in Ab loading among replicates than did the passive adsorption approach. Surface topography analysis revealed that a dextran coating reduced nonspecific antibody binding. Elemental analysis (XPS) was used to characterize the surface at different stages and showed that APBA molecules can bind upside-down on the surface. While upside-down antibodies likely remain functional, their elution behavior might differ from those bound in the desired way. Cell capture experiments show that the new surface has 43% better selectivity and 2.4-fold higher capture efficiency compared to a control surface of passively adsorbed Abs. This specific surface chemistry modification will allow the targeted capture of cells or analytes with the option of chemical detachment for further research and characterization.
Collapse
Affiliation(s)
- Elham Shirani
- School of Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
| | - Amir Razmjou
- Mineral Recovery Research Center (MRRC), School of Engineering, Edith Cowan University, Joondalup, Perth, Western Australia 6027, Australia
| | - Mohsen Asadnia
- School of Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
| | - Robert E Nordon
- Graduate School of Biomedical Engineering, University of New South Wales, Sydney, New South Wales 2052, Australia
| | - David W Inglis
- School of Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
| |
Collapse
|
|
7
|
Roscales S, Sánchez-Sancho F, Csáky AG. (Ph3P)AuCl-catalyzed homocoupling of arylboronic acids under benchtop conditions: Synthesis of biphenyls. MOLECULAR CATALYSIS 2023; 547:113281. [DOI: 10.1016/j.mcat.2023.113281] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
8
|
Haveric A, Haveric S, Hadzic M, Ezic J, Cetković T, Galic B. Moderate Toxicity of Potential Boron-containing Therapeutic, Dipotassium-trioxohydroxytetrafl uorotriborate -K2(B3O3F4OH) in Rats and Mice. BRAZ J PHARM SCI 2023; 59. [DOI: 10.1590/s2175-97902023e21384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
|
|
9
|
Barrón-González M, Montes-Aparicio AV, Cuevas-Galindo ME, Orozco-Suárez S, Barrientos R, Alatorre A, Querejeta E, Trujillo-Ferrara JG, Farfán-García ED, Soriano-Ursúa MA. Boron-containing compounds on neurons: Actions and potential applications for treating neurodegenerative diseases. J Inorg Biochem 2023; 238:112027. [PMID: 36345068 DOI: 10.1016/j.jinorgbio.2022.112027] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 09/27/2022] [Accepted: 10/10/2022] [Indexed: 11/06/2022]
Abstract
Boron-containing compounds (BCC) exert effects on neurons. After the expanding of both the identification and synthesis of new BCC, novel effects in living systems have been reported, many of these involving neuronal action. In this review, the actions of BCC on neurons are described; the effects have been inferred by boron deprivation or addition. Also, the effects can be related to those mediated by interaction on ionic channels, G-protein coupled receptors, or other receptors exerting modification on neuronal behavior. Additionally, BCC have exhibited effects by the modulation of inflammation or oxidative processes. BCC are expanding as drugs. Deprivation of boron sources from the diet shows the role of some natural BCC. However, the observations of several new synthesized compounds suggest their ability to act with attractive potency, efficacy, and long-term action on neuronal receptors or processes related with the origin and evolution of neurodegenerative processes. The details of BCC-target interactions are currently being elucidated in progress, as those observed from BCC-protein crystal complexes. Taking all of the above into account, the expansion is presumably near to having studies on the application of BCC as drugs on specific targets for treating neurodegenerative diseases.
Collapse
Affiliation(s)
- Mónica Barrón-González
- Academia de Fisiología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Alc. Miguel Hidalgo, 11340 Mexico City, Mexico; Departamento de Bioquímica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Alc. Miguel Hidalgo, 11340 Mexico City, Mexico
| | - Alexia V Montes-Aparicio
- Academia de Fisiología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Alc. Miguel Hidalgo, 11340 Mexico City, Mexico; Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, 06720 Mexico City, Mexico
| | - M Emilio Cuevas-Galindo
- Departamento de Bioquímica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Alc. Miguel Hidalgo, 11340 Mexico City, Mexico
| | - Sandra Orozco-Suárez
- Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, 06720 Mexico City, Mexico
| | - Rafael Barrientos
- Academia de Fisiología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Alc. Miguel Hidalgo, 11340 Mexico City, Mexico
| | - Alberto Alatorre
- Academia de Fisiología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Alc. Miguel Hidalgo, 11340 Mexico City, Mexico
| | - Enrique Querejeta
- Academia de Fisiología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Alc. Miguel Hidalgo, 11340 Mexico City, Mexico
| | - José G Trujillo-Ferrara
- Departamento de Bioquímica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Alc. Miguel Hidalgo, 11340 Mexico City, Mexico
| | - Eunice D Farfán-García
- Departamento de Bioquímica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Alc. Miguel Hidalgo, 11340 Mexico City, Mexico.
| | - Marvin A Soriano-Ursúa
- Academia de Fisiología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Alc. Miguel Hidalgo, 11340 Mexico City, Mexico.
| |
Collapse
|
|
10
|
Temel H, Atlan M, Ertas A, Yener I, Akdeniz M, Yazan Z, Yilmaz MA, Doganyigit Z, Okan A, Akyuz E. Cream production and biological in vivo/in vitro activity assessment of a novel boron-based compound derived from quercetin and phenyl boronic acid. J Trace Elem Med Biol 2022; 74:127073. [PMID: 36126542 DOI: 10.1016/j.jtemb.2022.127073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 08/09/2022] [Accepted: 09/11/2022] [Indexed: 11/24/2022]
Abstract
Boronic acids constitute an important class of synthetic intermediates due to their high chemical stability, ease of use, moderate organic Lewis acid properties, reduced reactivity profiles and numerous biological activities such as antibacterial and antioxidant. The present study documents the synthesis and characterization of a novel boronic ester compound (3,5,7-trihydroxy-2- (2-phenyl benzo [d] [1,3,2] dioxaborol-5-yl) -4H-chromen-4-a) which was derived from phenyl boronic acid and quercetin. The new boron-based compound was used in the cream formulation after evaluating its antioxidant, antibacterial, anti-enzyme, anticancer activities and electrochemical oxidation behaviour. Furthermore, the cream has been dermatologically and microbiologically tested. Also, histological evaluation of the agent was estimated on multiple rat organs by hematoxylin-eosin staining method. Antioxidant potential of the new compound was tested by ABTS cation radical (IC50: 0.11 ± 0.01 µg/mL), DPPH free radical scavenging (IC50: 0.14 ± 0.01 µg/mL), and CUPRAC (A0.5: 1.73 ± 0.16 µg/mL) methods, respectively. The compound determined to have a dominant antioxidant activity. In addition, the synthesized compound had no toxic effect on the healthy cell line (PDF), while having a very high (IC50: 18.76 ± 0.62 µg/mL) cytotoxic effect on the cancerous cell line (MCF-7). In general, the compound showed moderate acetylcholinesterase enzyme activity (IC50: 115.63 ± 1.16 µg/mL), high butyrylcholinesterase (IC50: 3.12 ± 0.04 µg/mL), antiurease (IC50: 1.10 ± 0.06 µg/mL), and antithyrosinase (IC50: 11.52 ± 0.46 µg/mL) enzyme activities. In addition, the compound was found to be effective against Escherichia coli (ATCC 25922) bacteria studied at concentrations of 6.50 mg/mL. Moreover, the test results of the boronic ester compound used in the cream formulation demonstrated that it was microbiologically and dermatologically appropriate. Histologic analysis showed that the control group and experimental group were at similar properties without significant change. The phenyl boronic acid derivative compound synthesized from quercetin may have higher biological activity potential than quercetin. Due to the high biological activity potential of the synthesized compound, it has the potential to be used in food, feed, pharmaceutical and cosmetic industries.
Collapse
Affiliation(s)
- Hamdi Temel
- Department of Chemistry, Institute of Science, Dicle University, 21280 Diyarbakir, Turkiye; Department of Medical Pharmacology, Faculty of Medicine, Yozgat Bozok University, 66000 Yozgat, Turkiye.
| | - Metin Atlan
- Department of Chemistry, Institute of Science, Dicle University, 21280 Diyarbakir, Turkiye
| | - Abdulselam Ertas
- Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, 21280 Diyarbakir, Turkiye
| | - Ismail Yener
- Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, 21280 Diyarbakir, Turkiye
| | - Mehmet Akdeniz
- The Council of Forensic Medicine, Ministry of Justice, 21100 Diyarbakir, Turkiye
| | - Zehra Yazan
- Department of Chemistry, Faculty of Science, Ankara University, 06100 Ankara, Turkiye
| | - Mustafa Abdullah Yilmaz
- Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, 21280 Diyarbakir, Turkiye
| | - Zuleyha Doganyigit
- Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, 66000, Yozgat, Turkiye
| | - Asli Okan
- Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, 66000, Yozgat, Turkiye
| | - Enes Akyuz
- Department of Biophysics, Faculty of International Medicine, University of Health Sciences, 34600 Istanbul, Turkiye
| |
Collapse
|
|
11
|
Farfán-García ED, Rosales-Hernández MC, Castillo-García EL, Abad-García A, Ruiz-Maciel O, Velasco-Silveyra LM, González-Muñiz AY, Andrade-Jorge E, Soriano-Ursúa MA. Identification and evaluation of boronic compounds ameliorating cognitive deficit in orchiectomized rats. J Trace Elem Med Biol 2022; 72:126979. [PMID: 35364473 DOI: 10.1016/j.jtemb.2022.126979] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 03/15/2022] [Accepted: 03/22/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Boron is a trace element with increasing importance in drug design. In this sense, boronic acids are emerging as therapeutic agents for several diseases. METHODS Herein, 3- and 4- acetamidophenylboronic acids and 4-acetamidophenylboronic acid pinacol ester were identified as potential inhibitors of acetylcholinesterase through docking assays on eel, rat, and human acetylcholinesterases indicating binding on the gorge region of the target enzymes. Then, these compounds were evaluated in vitro and in vivo. RESULTS It was found these compounds showed ability to inhibit acetylcholinesterase as competitive and non-competitive inhibitors. But also, these compounds were non-toxic to PC12 cells at micromolar concentration, and they have the ability to protect those cells against damage by amyloid-beta. CONCLUSIONS Noticeably, intraperitoneal administration of these boronic compounds to rats with the cognitive deficit induced by orchiectomy provided ameliorative effects on disrupted behavior and neuronal damage induced by hormonal deprivation. Additional approaches are required to evaluate the possibility of multiple mechanisms of action for the observed effects in the central nervous system.
Collapse
Affiliation(s)
- Eunice D Farfán-García
- Academia de Fisiología y Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340 México City, México.
| | - Martha C Rosales-Hernández
- Laboratorio de Biofísica y Biocatálisis. Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340 México City, México
| | - Emily L Castillo-García
- Academia de Fisiología y Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340 México City, México
| | - Antonio Abad-García
- Academia de Fisiología y Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340 México City, México
| | - Omar Ruiz-Maciel
- Departamento de Bioquímica y Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340 México City, México
| | - Luz M Velasco-Silveyra
- Academia de Fisiología y Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340 México City, México
| | - Alejandra Y González-Muñiz
- Laboratorio de Biofísica y Biocatálisis. Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340 México City, México
| | - Erik Andrade-Jorge
- Departamento de Bioquímica y Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340 México City, México
| | - Marvin A Soriano-Ursúa
- Academia de Fisiología y Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340 México City, México.
| |
Collapse
|
|
12
|
In vitro antifungal effect of phenylboronic and boric acid on Alternaria alternata. Arh Hig Rada Toksikol 2022; 73:83-87. [PMID: 35390244 PMCID: PMC8999588 DOI: 10.2478/aiht-2022-73-3620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 03/01/2022] [Indexed: 11/30/2022] Open
Abstract
The ascomycete fungus Alternaria alternata causes early blight, one of economically the most important tomato diseases. Due to frequent use of fungicides, A. alternata has developed resistance with negative economic and environmental consequences. Research of new ways to control fungal pathogens has turned its eye to environmentally friendly chemicals with low toxicity such as boronic acids. The aim of our study was therefore to test the antifungal effects of phenylboronic and boric acid in vitro on A. alternata. We isolated the pathogen from a symptomatic tomato plant and determined the minimum inhibitory concentration of phenylboronic and boric acid on A. alternata mycelial growth using the poisoned food technique. The antifungal effect was tested on a wide range of phenylboronic and boric acid concentrations (from 0.04 % to 0.3 %) applied separately to agar with mycelial disc of the pathogen. After five days of incubation, phenylboronic acid at low concentration (0.05 %) completely inhibited mycelial growth. Boric acid, in turn, did not significantly slow down mycelial growth but did reduce sporulation and confirmed its fungistatic effect. Our findings point to the potential use of phenylboronic acid to control phytopathogenic fungi. This is, to our knowledge, the first report on its antifungal effect on an agriculturally important pathogen in vitro. Moreover, since A. alternata is also a human pathogen, these results may have clinical ramifications.
Collapse
|
|
13
|
Synthesis and Characterization of 4-Formylphenylboronic Acid Cross-linked Chitosan Hydrogel with Dual Action: Glucose-Sensitivity and Controlled Insulin Release. CHINESE JOURNAL OF ANALYTICAL CHEMISTRY 2022. [DOI: 10.1016/j.cjac.2022.100092] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
|
|
14
|
Abad-García A, Ocampo-Néstor AL, Das BC, Farfán-García ED, Bello M, Trujillo-Ferrara JG, Soriano-Ursúa MA. Interactions of a boron-containing levodopa derivative on D 2 dopamine receptor and its effects in a Parkinson disease model. J Biol Inorg Chem 2022; 27:121-131. [PMID: 34806120 DOI: 10.1007/s00775-021-01915-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 11/01/2021] [Indexed: 02/07/2023]
Abstract
Levodopa is a cornerstone in Parkinson's disease treatment. Beneficial effects are mainly by binding on D2 receptors. Docking simulations of a set of compounds including well-known D2-ligands and a pool of Boron-Containing Compounds (BCC), particularly boroxazolidones with a tri/tetra-coordinated boron atom, were performed on the D2 Dopamine receptor (D2DR). Theoretical results yielded higher affinity of the compound DPBX, a Dopaboroxazolidone, than levodopa on D2DR. Essential interactions with residues in the third and sixth transmembrane domains of the D2DR appear to be crucial to induce and stabilize interactions in the active receptor state. Results from a motor performance evaluation of a murine model of Parkinson's disease agree with theoretical results, as DPBX showed similar efficacy to that of levodopa for diminishing MPTP-induced parkinsonism. This beneficial effect was disrupted with prior Risperidone (D2DR antagonist) administration, supporting the role of D2DR in the biological effect of DPBX. In addition, DPBX limited neuronal loss in substantia nigra in a similar manner to that of levodopa administration.
Collapse
Affiliation(s)
- Antonio Abad-García
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, s/n. Col. Casco de Santo Tomás, Del. Miguel Hidalgo, 11340, Mexico City, Mexico
| | - A Lilia Ocampo-Néstor
- Departamento de Nefrología, Hospital General de México "Dr. Eduardo Liceaga", Dr. Balmis 148, Alc. Cuauhtémoc, 06720, Mexico City, Mexico
| | - Bhaskar C Das
- Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, 11201-5497, USA
| | - Eunice D Farfán-García
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, s/n. Col. Casco de Santo Tomás, Del. Miguel Hidalgo, 11340, Mexico City, Mexico
| | - Martiniano Bello
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, s/n. Col. Casco de Santo Tomás, Del. Miguel Hidalgo, 11340, Mexico City, Mexico
| | - José G Trujillo-Ferrara
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, s/n. Col. Casco de Santo Tomás, Del. Miguel Hidalgo, 11340, Mexico City, Mexico
| | - Marvin A Soriano-Ursúa
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, s/n. Col. Casco de Santo Tomás, Del. Miguel Hidalgo, 11340, Mexico City, Mexico.
| |
Collapse
|
|
15
|
Abad-García A, Ocampo-Néstor AL, Das BC, Farfán-García ED, Bello M, Trujillo-Ferrara JG, Soriano-Ursúa MA. Interactions of a boron-containing levodopa derivative on D 2 dopamine receptor and its effects in a Parkinson disease model. J Biol Inorg Chem 2021. [PMID: 34806120 DOI: 10-1007/s00775-021-01915-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Levodopa is a cornerstone in Parkinson's disease treatment. Beneficial effects are mainly by binding on D2 receptors. Docking simulations of a set of compounds including well-known D2-ligands and a pool of Boron-Containing Compounds (BCC), particularly boroxazolidones with a tri/tetra-coordinated boron atom, were performed on the D2 Dopamine receptor (D2DR). Theoretical results yielded higher affinity of the compound DPBX, a Dopaboroxazolidone, than levodopa on D2DR. Essential interactions with residues in the third and sixth transmembrane domains of the D2DR appear to be crucial to induce and stabilize interactions in the active receptor state. Results from a motor performance evaluation of a murine model of Parkinson's disease agree with theoretical results, as DPBX showed similar efficacy to that of levodopa for diminishing MPTP-induced parkinsonism. This beneficial effect was disrupted with prior Risperidone (D2DR antagonist) administration, supporting the role of D2DR in the biological effect of DPBX. In addition, DPBX limited neuronal loss in substantia nigra in a similar manner to that of levodopa administration.
Collapse
Affiliation(s)
- Antonio Abad-García
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, s/n. Col. Casco de Santo Tomás, Del. Miguel Hidalgo, 11340, Mexico City, Mexico
| | - A Lilia Ocampo-Néstor
- Departamento de Nefrología, Hospital General de México "Dr. Eduardo Liceaga", Dr. Balmis 148, Alc. Cuauhtémoc, 06720, Mexico City, Mexico
| | - Bhaskar C Das
- Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, 11201-5497, USA
| | - Eunice D Farfán-García
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, s/n. Col. Casco de Santo Tomás, Del. Miguel Hidalgo, 11340, Mexico City, Mexico
| | - Martiniano Bello
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, s/n. Col. Casco de Santo Tomás, Del. Miguel Hidalgo, 11340, Mexico City, Mexico
| | - José G Trujillo-Ferrara
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, s/n. Col. Casco de Santo Tomás, Del. Miguel Hidalgo, 11340, Mexico City, Mexico
| | - Marvin A Soriano-Ursúa
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, s/n. Col. Casco de Santo Tomás, Del. Miguel Hidalgo, 11340, Mexico City, Mexico.
| |
Collapse
|
|
16
|
Wright CC, Wooton KM, Twiss KC, Newman ET, Rasbury ET. Boron Isotope Analysis Reveals Borate Selectivity in Seaweeds. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2021; 55:12724-12730. [PMID: 34473928 DOI: 10.1021/acs.est.1c02860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
The role of boron in terrestrial plant physiology is diverse and increasingly well understood, but its role in marine aquatic eukaryotes is less clear. Our research reveals a distinctive and large offset in boron isotopes from seawater, irrespective of seaweed type or season. We show that the offset is consistent with the incorporation of borate from seawater. Boron is a known micronutrient in plants but very few studies have used boron isotopes to investigate boron's role in plant physiology. Seaweed, as the most primitive multicellular plant, has an important role in investigating wider plant adaptations that use boron to meet functional needs. Furthermore, seaweed and other plants are a key base nutrient provider in food webs, supplying boron to consumers and playing a critical role in boron environmental cycling.
Collapse
Affiliation(s)
- Carrie C Wright
- Department of Geosciences, Stony Brook University, Stony Brook, New York 11794, United States
| | - Kathleen M Wooton
- Department of Geosciences, Stony Brook University, Stony Brook, New York 11794, United States
| | - Katheryn C Twiss
- Department of Anthropology, Stony Brook University, Stony Brook, New York 11794, United States
| | - Elizabeth T Newman
- Department of History, Stony Brook University, Stony Brook, New York 11794, United States
| | - E Troy Rasbury
- Department of Geosciences, Stony Brook University, Stony Brook, New York 11794, United States
| |
Collapse
|
|
17
|
Martínez-Cerón S, Gutiérrez-Nágera NA, Mirzaeicheshmeh E, Cuevas-Hernández RI, Trujillo-Ferrara JG. Phenylbenzothiazole derivatives: effects against a Trypanosoma cruzi infection and toxicological profiles. Parasitol Res 2021; 120:2905-2918. [PMID: 34195872 DOI: 10.1007/s00436-021-07137-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 03/22/2021] [Indexed: 11/29/2022]
Abstract
Current treatments for Chagas disease have a limited impact during the chronic stage and trigger severe side effects. Treatments target Trypanosoma cruzi, the etiological agent of the disease. The aims of this study were to evaluate the trypanocidal activity of four 2-phenylbenzothiazole derivatives (BZT1-4) in vitro by using the infectious and non-infectious forms of T. cruzi (trypomastigotes and epimastigotes, respectively) and to test the most promising compound (BZT4) in vivo in mice. Additionally, the toxicological profile and possible neuronal damage were examined. In relation to trypomastigotes, BZT4 was more selective and effective than the reference drug (benznidazole) during this infective stage, apparently due to the synergistic action of the CF3 and COOH substituents in the molecule. During the first few hours post-administration of BZT4, parasitemia decreased by 40% in an in vivo model of short-term treatment, but parasite levels later returned to the basal state. In the long-term assessment, the compound did not produce a significant antiparasitic effect, only attaining a 30% reduction in parasitemia by day 20 with the dose of 16 mg/kg. The toxicity test was based on repeated dosing of BZT4 (administered orally) during 21 days, which did not cause liver damage. However, the compound altered the concentration of proteins and the proteinic profile of neuronal cells in vitro, perhaps leading to an effect on the central nervous system. Further research on the low trypanocidal activity in vivo compared to the better in vitro effect could possibly facilitate molecular redesign to improve trypanocidal activity.
Collapse
Affiliation(s)
- Sarai Martínez-Cerón
- Laboratory of Biochemistry Research, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón S/N, Casco de Santo Tomas, Miguel Hidalgo, 11340, Mexico City, Mexico
| | - Nora Andrea Gutiérrez-Nágera
- Instituto Nacional de Medicina Genómica - INMEGEN, Av. Periférico Sur No. 4809, Col. Arenal Tepepan, Tlalpan, 14610, Mexico City, Mexico
| | - Elaheh Mirzaeicheshmeh
- Instituto Nacional de Medicina Genómica - INMEGEN, Av. Periférico Sur No. 4809, Col. Arenal Tepepan, Tlalpan, 14610, Mexico City, Mexico
| | - Roberto I Cuevas-Hernández
- Laboratory of Biochemistry Research, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón S/N, Casco de Santo Tomas, Miguel Hidalgo, 11340, Mexico City, Mexico.
| | - José G Trujillo-Ferrara
- Laboratory of Biochemistry Research, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón S/N, Casco de Santo Tomas, Miguel Hidalgo, 11340, Mexico City, Mexico.
| |
Collapse
|
|
18
|
Arabi M, Ostovan A, Li J, Wang X, Zhang Z, Choo J, Chen L. Molecular Imprinting: Green Perspectives and Strategies. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2021; 33:e2100543. [PMID: 34145950 DOI: 10.1002/adma.202100543] [Citation(s) in RCA: 342] [Impact Index Per Article: 85.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/25/2021] [Indexed: 05/04/2023]
Abstract
Advances in revolutionary technologies pose new challenges for human life; in response to them, global responsibility is pushing modern technologies toward greener pathways. Molecular imprinting technology (MIT) is a multidisciplinary mimic technology simulating the specific binding principle of enzymes to substrates or antigens to antibodies; along with its rapid progress and wide applications, MIT faces the challenge of complying with green sustainable development requirements. With the identification of environmental risks associated with unsustainable MIT, a new aspect of MIT, termed green MIT, has emerged and developed. However, so far, no clear definition has been provided to appraise green MIT. Herein, the implementation process of green chemistry in MIT is demonstrated and a mnemonic device in the form of an acronym, GREENIFICATION, is proposed to present the green MIT principles. The entire greenificated imprinting process is surveyed, including element choice, polymerization implementation, energy input, imprinting strategies, waste treatment, and recovery, as well as the impacts of these processes on operator health and the environment. Moreover, assistance of upgraded instrumentation in deploying greener goals is considered. Finally, future perspectives are presented to provide a more complete picture of the greenificated MIT road map and to pave the way for further development.
Collapse
Affiliation(s)
- Maryam Arabi
- CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Shandong Key Laboratory of Coastal Environmental Processes, Research Center for Coastal Environmental Engineering and Technology, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China
| | - Abbas Ostovan
- CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Shandong Key Laboratory of Coastal Environmental Processes, Research Center for Coastal Environmental Engineering and Technology, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China
| | - Jinhua Li
- CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Shandong Key Laboratory of Coastal Environmental Processes, Research Center for Coastal Environmental Engineering and Technology, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China
- Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China
| | - Xiaoyan Wang
- School of Pharmacy, Binzhou Medical University, Yantai, 264003, China
| | - Zhiyang Zhang
- CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Shandong Key Laboratory of Coastal Environmental Processes, Research Center for Coastal Environmental Engineering and Technology, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China
- Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China
| | - Jaebum Choo
- Department of Chemistry, Chung-Ang University, Seoul, 06974, South Korea
| | - Lingxin Chen
- CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Shandong Key Laboratory of Coastal Environmental Processes, Research Center for Coastal Environmental Engineering and Technology, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China
- Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China
- School of Environmental & Municipal Engineering, Qingdao University of Technology, Qingdao, 266033, China
| |
Collapse
|
|
19
|
Abstract
BACKGROUND Hypoglycemia, the condition of low blood sugar, is a common occurance in people with diabetes using insulin therapy. Protecting against hypoglycaemia by engineering an insulin preparation that can auto-adjust its biological activity to fluctuating blood glucose levels has been pursued since the 1970s, but despite numerous publications, no system that works well enough for practical use has reached clinical practise. SCOPE OF REVIEW This review will summarise and scrutinise known approaches for producing glucose-sensitive insulin therapies. Notably, systems described in patent applications will be extensively covered, which has not been the case for earlier reviews of this area. MAJOR CONCLUSIONS The vast majority of published systems are not suitable for product development, but a few glucose-sensitive insulin concepts have recently reached clinical trials, and there is hope that glucose-sensitive insulin will become available to people with diabetes in the near future.
Collapse
Affiliation(s)
- Thomas Hoeg-Jensen
- Research Chemistry, Novo Nordisk A/S, Novo Nordisk Park H5.S.05, DK-2720 Maaloev, Denmark.
| |
Collapse
|
|
20
|
Wright JS, Scott PJH, Steel PG. Iridium-Catalysed C-H Borylation of Heteroarenes: Balancing Steric and Electronic Regiocontrol. Angew Chem Int Ed Engl 2021; 60:2796-2821. [PMID: 32202024 PMCID: PMC7894576 DOI: 10.1002/anie.202001520] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 03/09/2020] [Indexed: 12/19/2022]
Abstract
The iridium-catalysed borylation of aromatic C-H bonds has become the preferred method for the synthesis of aromatic organoboron compounds. The reaction is highly efficient, tolerant of a broad range of substituents and can be applied to both carbocyclic and heterocyclic substrates. The regioselectivity of C-H activation is dominated by steric considerations and there have been considerable efforts to develop more selective processes for less constrained substrates. However, most of these have focused on benzenoid-type substrates and in contrast, heteroarenes remain much desired but more challenging substrates with the position and/or nature of the heteroatom(s) significantly affecting reactivity and regioselectivity. This review will survey the borylation of heteroarenes, focusing on the influence of steric and electronic effects on regiochemical outcome and, by linking to current mechanistic understandings, will provide insights to what is currently possible and where further developments are required.
Collapse
Affiliation(s)
- Jay S. Wright
- Department of ChemistryUniversity of DurhamScience Laboratories, South Road DurhamDurhamDH1 3LEUK
- Department of RadiologyUniversity of MichiganAnn ArborMichiganUSA
| | | | - Patrick G. Steel
- Department of ChemistryUniversity of DurhamScience Laboratories, South Road DurhamDurhamDH1 3LEUK
| |
Collapse
|
|
21
|
Hadrup N, Frederiksen M, Sharma AK. Toxicity of boric acid, borax and other boron containing compounds: A review. Regul Toxicol Pharmacol 2021; 121:104873. [PMID: 33485927 DOI: 10.1016/j.yrtph.2021.104873] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 01/06/2021] [Accepted: 01/18/2021] [Indexed: 01/14/2023]
Abstract
Boron, often in the form of boric acid, is widely used as a flame retardant in insulation products, and although humans ingest boron through food, high exposure may lead to unwanted health effects. We assessed the toxicity of boric acid, borax and other forms of boron, after inhalation, dermal and oral exposure. After oral exposure, boron is absorbed over the gastrointestinal tract. Intact skin seems to pose a more effective barrier to boron than compromised skin. Boron excretion seems to mainly occur via the urine, although after skin exposure boron has been demonstrated in bile and gastrointestinal contents. Inhalation toxicity data are sparse, but one animal study showed reduced foetal weight after inhalation of cellulose that had a boric acid content of 20%. Skin exposure to boric acid has proven fatal in some cases, and the range of toxicity effects include abdominal as well as local effects on the skin. Fatalities from boric acid also have occurred after oral ingestion, and the endpoints in animals are weight loss and reproductive toxicity. Concerning genotoxicity studies, the overall picture indicates that boron-containing compounds are not genotoxic. There was no evidence of the carcinogenicity of boric acid in a 2-year study in mice.
Collapse
Affiliation(s)
- Niels Hadrup
- National Research Centre for the Working Environment, Copenhagen, DK, 2100, Denmark.
| | - Marie Frederiksen
- National Research Centre for the Working Environment, Copenhagen, DK, 2100, Denmark
| | - Anoop K Sharma
- Division for Risk Assessment and Nutrition, Group for Chemical Risk Assessment and GMO, National Food Institute, Technical University of Denmark, Denmark.
| |
Collapse
|
|
22
|
|
|
23
|
Wright JS, Scott PJH, Steel PG. Iridium‐katalysierte C‐H‐Borylierung von Heteroarenen: Eine Balance zwischen sterischer and elektronischer Regiokontrolle. Angew Chem Int Ed Engl 2020. [DOI: 10.1002/ange.202001520] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Jay S. Wright
- Department of Chemistry University of Durham Science Laboratories, South Road Durham Durham DH1 3LE Großbritannien
- Department of Radiology University of Michigan Ann Arbor Michigan USA
| | - Peter J. H. Scott
- Department of Radiology University of Michigan Ann Arbor Michigan USA
| | - Patrick G. Steel
- Department of Chemistry University of Durham Science Laboratories, South Road Durham Durham DH1 3LE Großbritannien
| |
Collapse
|
|
24
|
Sarkar W, Bhowmik A, Das S, Sulekha AB, Mishra A, Deb I. Iridium-catalyzed direct C-H arylation of cyclic N-sulfonyl ketimines with arylsiloxanes at ambient temperature. Org Biomol Chem 2020; 18:7074-7078. [PMID: 32691811 DOI: 10.1039/d0ob01212b] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
An iridium-catalyzed ortho-selective C-H arylation of cyclic N-sulfonyl ketimines has been achieved with environmentally benign aryl siloxanes. The reaction is highly efficient and proceeds at ambient temperature which is the key feature of the methodology considering the weak coordination nature of the substrate as well as the sluggish reactivity of siloxanes. A wide array of pharmaceutically relevant novel biaryls has been synthesized under operationally simple conditions.
Collapse
Affiliation(s)
- Writhabrata Sarkar
- Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4-Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
| | - Arup Bhowmik
- Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4-Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
| | - Sumit Das
- Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4-Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India. and Academy of Scientific and Innovative Research (AcSIR), India
| | - Aiswarya Balaram Sulekha
- Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4-Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
| | - Aniket Mishra
- Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4-Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
| | - Indubhusan Deb
- Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4-Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
| |
Collapse
|
|
25
|
Üstündağ FD, Ünal İ, Cansız D, Üstündağ ÜV, Subaşat HK, Alturfan AA, Tiber PM, Emekli-Alturfan E. 3-Pyridinylboronic acid normalizes the effects of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure in zebrafish embryos. Drug Chem Toxicol 2020; 45:947-954. [PMID: 32693643 DOI: 10.1080/01480545.2020.1795189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that damages dopaminergic neurons. Zebrafish has been shown to be a suitable model organism to investigate the molecular pathways in the pathogenesis of Parkinson's disease and also for potential therapeutic agent research. Boron has been shown to play an important role in the neural activity of the brain. Boronic acids are used in combinatorial approaches in drug design and discovery. The effect of 3-pyridinylboronic acid which is an important sub-class of heterocyclic boronic acids has not been evaluated in case of MPTP exposure in zebrafish embryos. Accordingly, this study was designed to investigate the effects of 3-pyridinylboronic acid on MPTP exposed zebrafish embryos focusing on the molecular pathways related to neurodegeneration and apoptosis by RT-PCR. Zebrafish embryos were exposed to MPTP (800 μM); MPTP + Low Dose 3-Pyridinylboronic acid (50 μM) (MPTP + LB) and MPTP + High Dose 3-Pyridinylboronic acid (100 μM) (MPTP + HB) in well plates for 72 hours post fertilization. Results of our study showed that MPTP induced a P53 dependent and Bax mediated apoptosis in zebrafish embryos and 3-pyridinylboronic acid restored the locomotor activity and gene expressions related to mitochondrial dysfunction and oxidative stress due to the deleterious effects of MPTP, in a dose-dependent manner.
Collapse
Affiliation(s)
- Fümet Duygu Üstündağ
- Faculty of Medicine, Department of Biophysics, Marmara University, Istanbul, Turkey
| | - İsmail Ünal
- Faculty of Dentistry, Department of Basic Medical Sciences, Marmara University, Istanbul, Turkey
| | - Derya Cansız
- Faculty of Medicine, Department of Biochemistry, Istanbul University-Cerrahpaşa, Istanbul, Turkey
| | - Ünsal Veli Üstündağ
- Faculty of Medicine, Medical Biochemistry, Department Medipol University, Istanbul, Turkey
| | - Hülya Kara Subaşat
- Graduate School of Natural and Applied Sciences, Department of Energy, Mugla Sıtkı Kocman University, Muğla, Turkey
| | - A Ata Alturfan
- Faculty of Medicine, Department of Biochemistry, Istanbul University-Cerrahpaşa, Istanbul, Turkey
| | - Pınar Mega Tiber
- Faculty of Medicine, Department of Biophysics, Marmara University, Istanbul, Turkey
| | - Ebru Emekli-Alturfan
- Faculty of Dentistry, Department of Basic Medical Sciences, Marmara University, Istanbul, Turkey
| |
Collapse
|
|
26
|
Zhu H, Mishra R, Yuan L, Abdul Salam SF, Liu J, Gray G, Sterling AD, Wunderlich M, Landero-Figueroa J, Garrett JT, Merino EJ. Oxidative Cyclization-Induced Activation of a Phosphoinositide 3-Kinase Inhibitor for Enhanced Selectivity of Cancer Chemotherapeutics. ChemMedChem 2019; 14:1933-1939. [PMID: 31696673 DOI: 10.1002/cmdc.201900481] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 10/03/2019] [Indexed: 12/18/2022]
Abstract
In this work, we designed a prodrug that reacts with cellular oxidative equivalents leading to ether cleavage and cyclization to release an active phosphatidylinositol 3-kinase (PI3K) inhibitor. We show that the compound reduces affinity for PI3KA relative to the PI3K inhibitor, is slow to intercellularly oxidize, and is resistant to liver microsomes. We observed modest activity in untreated acute myeloid leukemia cells and 14-fold selectivity relative to non-cancerous cells. The cellular activity of the compound can be modulated by the addition of antioxidants or oxidants, indicating the compound activity is sensitive to cellular reactive oxygen species (ROS) state. Co-treatment with cytosine arabinoside or doxorubicin was used to activate the compound inside cells. We observed strong synergistic activity specifically in acute myeloid leukemia (AML) cancer cells with an increase in selective anticancer activity of up to 90-fold. Thus, these new self-cyclizing compounds can be used to increase the selectivity of anticancer agents.
Collapse
Affiliation(s)
- Haizhou Zhu
- Figueroa, Prof. Dr. Edward. J. Merino* Department of Chemistry, McMicken College of Arts and Sciences, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Rosalin Mishra
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Long Yuan
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Safnas F Abdul Salam
- Figueroa, Prof. Dr. Edward. J. Merino* Department of Chemistry, McMicken College of Arts and Sciences, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Jing Liu
- Figueroa, Prof. Dr. Edward. J. Merino* Department of Chemistry, McMicken College of Arts and Sciences, University of Cincinnati, Cincinnati, OH 45221, USA
| | - George Gray
- Figueroa, Prof. Dr. Edward. J. Merino* Department of Chemistry, McMicken College of Arts and Sciences, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Alyssa D Sterling
- Figueroa, Prof. Dr. Edward. J. Merino* Department of Chemistry, McMicken College of Arts and Sciences, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Mark Wunderlich
- Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45221, USA
| | - Julio Landero-Figueroa
- Figueroa, Prof. Dr. Edward. J. Merino* Department of Chemistry, McMicken College of Arts and Sciences, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Joan T Garrett
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Edward J Merino
- Figueroa, Prof. Dr. Edward. J. Merino* Department of Chemistry, McMicken College of Arts and Sciences, University of Cincinnati, Cincinnati, OH 45221, USA
| |
Collapse
|
|
27
|
Baldwin AF, North R, Eisenbeis S. Trace Level Quantification of Derivatized Boronic Acids by LC/MS/MS. Org Process Res Dev 2019. [DOI: 10.1021/acs.oprd.8b00377] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Aaron F. Baldwin
- Pharmaceutical Sciences Small Molecule †Analytical Research & Development and ‡Chemical Research & Development, Pfizer, Eastern Point Road, Groton, Connecticut 06340, United States
| | - Robert North
- Pharmaceutical Sciences Small Molecule †Analytical Research & Development and ‡Chemical Research & Development, Pfizer, Eastern Point Road, Groton, Connecticut 06340, United States
| | - Shane Eisenbeis
- Pharmaceutical Sciences Small Molecule †Analytical Research & Development and ‡Chemical Research & Development, Pfizer, Eastern Point Road, Groton, Connecticut 06340, United States
| |
Collapse
|
|
28
|
Soriano-Ursúa MA, Farfán-García ED, Geninatti-Crich S. Turning Fear of Boron Toxicity into Boron-containing Drug Design. Curr Med Chem 2019; 26:5005-5018. [PMID: 30919770 DOI: 10.2174/0929867326666190327154954] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 01/24/2019] [Accepted: 02/08/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Despite the historical employment of boron-containing compounds (BCCs) with medicinal purposes, the reported cases of BCC toxicity in humans during the twentieth-century drived us towards a "boron-withdrawal" period. Fortunately, the use of boric acid for specific purposes remains, and the discovery of natural BCCs with biological action attractive for therapeutic purposes as well as the introduction of some new BCCs for clinical use has reactivated the interest in studying the properties of these BCCs. METHODS We carried out a structured search of bibliographic databases for scientific peerreviewed research literature regarding boron toxicity and linked that information to that of BCCs in drug design and development. A deductive qualitative content analysis methodology was applied to analyse the interventions and findings of the included studies using a theoretical outline. RESULTS This review recapitulates the following on a timeline: the boron uses in medicine, the data known about the toxicological profiles of some BCCs, the pharmacological properties of some BCCs that are employed in cancer and infectious disease therapies, and the known properties of BCCs recently introduced into clinical assays as well as the identification of their structure-activity relationships for toxicity and therapeutic use. Then, we discuss the use of new approaches taking advantage of some toxicological data to identify potent and efficient BCCs for prevention and therapy while limiting their toxic effects. CONCLUSION Data for boron toxicity can be strategically used for boron-containing drug design.
Collapse
Affiliation(s)
- Marvin A Soriano-Ursúa
- Departamentos de Fisiologia, Bioquimica y Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Plan de San Luis y Diaz Miron s/n, 11340, Mexico City,Mexico
| | - Eunice D Farfán-García
- Departamentos de Fisiologia, Bioquimica y Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Plan de San Luis y Diaz Miron s/n, 11340, Mexico City,Mexico
| | - Simonetta Geninatti-Crich
- Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Centro, Imaging Molecolare, Universita di Torino, via Nizza 52, Torino, 10126,Italy
| |
Collapse
|
|
29
|
López-Cabrera Y, Castillo-García EL, Altamirano-Espino JA, Pérez-Capistran T, Farfán-García ED, Trujillo-Ferrara JG, Soriano-Ursúa MA. Profile of three boron-containing compounds on the body weight, metabolism and inflammatory markers of diabetic rats. J Trace Elem Med Biol 2018; 50:424-429. [PMID: 30262315 DOI: 10.1016/j.jtemb.2018.08.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 08/29/2018] [Accepted: 08/31/2018] [Indexed: 02/07/2023]
Abstract
It has been reported that boron induces changes in carbohydrate and lipid metabolism, body weight and inflammatory processes. This is relevant to the biomedical field due to the requirement for developing therapeutic tools with potential application in metabolic disorders affecting humankind. However, most of the reported data from both humans and animals were obtained after boron was administered as borax or boric acid. In this work, we determined the effects of boric, cyclohexylboronic (CHB) and phenylboronic (PBA) acids (10 mg/kg of body weight/daily for two weeks) on the body weight, metabolism and inflammatory markers in the blood of control, fat-feeding and experimental diabetic rats. In particular, we observed the effects of the administration of these compounds on glycaemia and cholesterol, triglyceride, insulin, IL-6 and C-reactive protein levels, as well as visceral fat and body weight. We found different profiles for each boron-containing compound: boric acid induced decreasing body weight, insulin and IL-6 levels; CHB administration induced an increase in body weight and cholesterol but decreased IL-6 levels; and PBA administration induced a decrease in visceral fat and glucose and insulin levels. These results can improve the understanding of boron as a metabolic regulator and help develop new potential strategies to use compounds with this trace element for therapeutic purposes.
Collapse
Affiliation(s)
- Yessica López-Cabrera
- Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - Emily L Castillo-García
- Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - José A Altamirano-Espino
- Departamento de Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - Teresa Pérez-Capistran
- Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - Eunice D Farfán-García
- Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico; Departamento de Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - José G Trujillo-Ferrara
- Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - Marvin A Soriano-Ursúa
- Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico.
| |
Collapse
|
|
30
|
Khaliq H, Juming Z, Ke-Mei P. The Physiological Role of Boron on Health. Biol Trace Elem Res 2018; 186:31-51. [PMID: 29546541 DOI: 10.1007/s12011-018-1284-3] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 02/21/2018] [Indexed: 12/20/2022]
Abstract
Boron is an essential mineral that plays an important role in several biological processes. Boron is required for growth of plants, animals, and humans. There are increasing evidences of this nutrient showing a variety of pleiotropic effects, ranging from anti-inflammatory and antioxidant effects to the modulation of different body systems. In the past few years, the trials showed disease-related polymorphisms of boron in different species, which has drawn attention of scientists to the significance of boron to health. Low boron profile has been related with poor immune function, increased risk of mortality, osteoporosis, and cognitive deterioration. High boron status revealed injury to cell and toxicity in different animals and humans. Some studies have shown some benefits of higher boron status, but findings have been generally mixed, which perhaps accentuates the fact that dietary intake will benefit only if supplemental amount is appropriate. The health benefits of boron are numerous in animals and humans; for instance, it affects the growth at safe intake. Central nervous system shows improvement and immune organs exhibit enhanced immunity with boron supplementation. Hepatic metabolism also shows positive changes in response to dietary boron intake. Furthermore, animals and human fed diets supplemented with boron reveal improved bone density and other benefits including embryonic development, wound healing, and cancer therapy. It has also been reported that boron affects the metabolism of several enzymes and minerals. In the background of these health benefits, low or high boron status is giving cause for concern. Additionally, researches are needed to further elucidate the mechanisms of boron effects, and determine the requirements in different species.
Collapse
Affiliation(s)
- Haseeb Khaliq
- College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China
| | - Zhong Juming
- College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China
- College of Veterinary Medicine, Auburn University, Auburn, AL, USA
| | - Peng Ke-Mei
- College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
| |
Collapse
|
|
31
|
Bello M, Guadarrama-García C, Velasco-Silveyra LM, Farfán-García ED, Soriano-Ursúa MA. Several effects of boron are induced by uncoupling steroid hormones from their transporters in blood. Med Hypotheses 2018; 118:78-83. [PMID: 30037620 DOI: 10.1016/j.mehy.2018.06.024] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Accepted: 06/19/2018] [Indexed: 02/07/2023]
Abstract
Boron is increasingly added to food supplements due to multiple effects that have been reported in mammals after boric acid administration. Among these effects are inflammatory process control, bone and muscle strength enhancement, protein expression regulation, and a decreased risk of developing some pathologies in which these processes are key, such as osteoporosis, dermatological inflammatory non-infectious maladies and diseases affecting the central nervous system. Experimental data have suggested that steroid hormone levels in plasma change after boric acid administration, but a clear mechanism behind these variations has not been established. We analyzed possibilities for these changes and hypothesized that boric acid disrupts the interactions between steroid hormones and several carriers in plasma. In particular, we proposed that there is an uncoupling of the interactions between sex hormone binding globulin (SHBG) and estrogens and testosterone and that there are alterations in the binding of hydrophobic ligands by other carrier proteins in plasma. Further experimental and computational studies are required to support the hypothesis that boric acid and probably other boron-containing compounds can displace steroid hormones from their plasma carriers. If such phenomena are confirmed, boron administration with a clear mechanism could be employed as a therapeutic agent in several diseases or physiological events that require modulation of steroid hormone levels in plasma.
Collapse
Affiliation(s)
- Martiniano Bello
- Laboratorio de Modelado Molecular y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 México City, Mexico
| | - Concepción Guadarrama-García
- Laboratorio de Modelado Molecular y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 México City, Mexico; Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 México City, Mexico
| | - Luz M Velasco-Silveyra
- Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 México City, Mexico
| | - Eunice D Farfán-García
- Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 México City, Mexico
| | - Marvin A Soriano-Ursúa
- Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 México City, Mexico.
| |
Collapse
|
|
32
|
Segura-Uribe JJ, Farfán-García ED, Guerra-Araiza C, Ciprés-Flores FJ, García-dela Torre P, Soriano-Ursúa MA. Differences in brain regions of three mice strains identified by label-free micro-Raman. SPECTROSCOPY LETTERS 2018; 51:356-366. [DOI: 10.1080/00387010.2018.1473883] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2017] [Accepted: 05/03/2018] [Indexed: 02/07/2023]
Affiliation(s)
- Julia Jeanett Segura-Uribe
- Departamento de Fisiología, Departamento de Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
- Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades. Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Eunice Dalet Farfán-García
- Departamento de Fisiología, Departamento de Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
| | - Christian Guerra-Araiza
- Unidad de Investigación Médica en Farmacología, Hospital de Especialidades. Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Fabiola Jimena Ciprés-Flores
- Departamento de Fisiología, Departamento de Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
| | - Paola García-dela Torre
- Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades. Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Marvin Antonio Soriano-Ursúa
- Departamento de Fisiología, Departamento de Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
| |
Collapse
|
|
33
|
BORON PREPARATIONS IN PSYCHIATRY AND NEUROLOGY: THEIR RISE, FALL AND RENEWED INTEREST. ACTA BIOMEDICA SCIENTIFICA 2018. [DOI: 10.29413/abs.2018-3.4.13] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
The use of boron preparations (borax and boric acid) in medicine began long before their isolation in pure form. The mineral water of boron-containing sources has been historically used to treat skin diseases, to wash eyes, to disinfect wounds, etc. Also, what is of interest in the context of this article, boron-containing waters were used as calming, anti- anxiety, anticonvulsant and sleep-promoting remedy. In 1777, boric acid was first isolated from the mineral water of a healing spring source in Florence. Historically, first name of this compound was sal sedativum (“soothing salt”). However, the discovery of boron toxicity led to the cessation of its internal use. In recent decades, it has been found that boron is a microelement necessary for many metabolic processes in the body. It affects memory, cognitive functions, anxiety level, sleep, mood, regulates calcium and magnesium exchange, metabolism of vitamin D and sex steroids. It has been shown that some cases of treatment resistance to standard therapy, for example in epilepsy, anxiety and depression, are related to boron deficiency. In this regard, interest in the use of boron preparations in psychiatry and neurology, but in much smaller doses and on new scientific grounds, flared up again.
Collapse
|
|
34
|
Zegota MM, Wang T, Seidler C, Wah Ng DY, Kuan SL, Weil T. "Tag and Modify" Protein Conjugation with Dynamic Covalent Chemistry. Bioconjug Chem 2018; 29:2665-2670. [PMID: 29949347 DOI: 10.1021/acs.bioconjchem.8b00358] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The development of small protein tags that exhibit bioorthogonality, bond stability, and reversibility, as well as biocompatibility, holds great promise for applications in cellular environments enabling controlled drug delivery or for the construction of dynamic protein complexes in biological environments. Herein, we report the first application of dynamic covalent chemistry both for purification and for reversible assembly of protein conjugates using interactions of boronic acid with diols and salicylhydroxamates. Incorporation of the boronic acid (BA) tag was performed in a site-selective fashion by applying disulfide rebridging strategy. As an example, a model protein enzyme (lysozyme) was modified with the BA tag and purified using carbohydrate-based column chromatography. Subsequent dynamic covalent "click-like" bioconjugation with a salicylhydroxamate modified fluorescent dye (BODIPY FL) was accomplished while retaining its original enzymatic activity.
Collapse
Affiliation(s)
- Maksymilian Marek Zegota
- Max-Planck Institute for Polymer Research , Ackermannweg 10 , 55128 Mainz , Germany.,Institute of Inorganic Chemistry I , University of Ulm , Albert-Einstein-Allee 11 , 89081 Ulm , Germany
| | - Tao Wang
- Institute of Inorganic Chemistry I , University of Ulm , Albert-Einstein-Allee 11 , 89081 Ulm , Germany.,School of Materials Science and Engineering , Southwest Jiaotong University , 610031 Chengdu , P.R. China
| | - Christiane Seidler
- Max-Planck Institute for Polymer Research , Ackermannweg 10 , 55128 Mainz , Germany.,Institute of Inorganic Chemistry I , University of Ulm , Albert-Einstein-Allee 11 , 89081 Ulm , Germany
| | - David Yuen Wah Ng
- Max-Planck Institute for Polymer Research , Ackermannweg 10 , 55128 Mainz , Germany.,Institute of Inorganic Chemistry I , University of Ulm , Albert-Einstein-Allee 11 , 89081 Ulm , Germany
| | - Seah Ling Kuan
- Max-Planck Institute for Polymer Research , Ackermannweg 10 , 55128 Mainz , Germany.,Institute of Inorganic Chemistry I , University of Ulm , Albert-Einstein-Allee 11 , 89081 Ulm , Germany
| | - Tanja Weil
- Max-Planck Institute for Polymer Research , Ackermannweg 10 , 55128 Mainz , Germany.,Institute of Inorganic Chemistry I , University of Ulm , Albert-Einstein-Allee 11 , 89081 Ulm , Germany
| |
Collapse
|
|
35
|
Zhang X, Xu G, Gadora K, Cheng H, Peng J, Ma Y, Guo Y, Chi C, Zhou J, Ding Y. Dual-sensitive chitosan derivative micelles for site-specific drug release in the treatment of chicken coccidiosis. RSC Adv 2018; 8:14515-14526. [PMID: 35540782 PMCID: PMC9079931 DOI: 10.1039/c8ra02144a] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Accepted: 04/02/2018] [Indexed: 12/17/2022] Open
Abstract
Here, we report a “dual-sensitive” drug delivery platform packaged with anti-coccidia drug diclazuril (DIC) applied in the field of intestinal-targeted administration.
Collapse
|
|
36
|
Marasovic M, Ivankovic S, Stojkovic R, Djermic D, Galic B, Milos M. In vitro and in vivo antitumour effects of phenylboronic acid against mouse mammary adenocarcinoma 4T1 and squamous carcinoma SCCVII cells. J Enzyme Inhib Med Chem 2017; 32:1299-1304. [PMID: 29072095 PMCID: PMC6010135 DOI: 10.1080/14756366.2017.1384823] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 09/19/2017] [Accepted: 09/21/2017] [Indexed: 02/04/2023] Open
Abstract
The cytotoxic activity of phenylboroxine acid was evaluated in vitro on mouse mammary adenocarcinoma 4T1, mouse squamous cell carcinoma SCCVII, hamster lung fibroblast V79 and mouse dermal fibroblasts L929 cell lines. The cytotoxic effects were dose dependent for all tested tumour and non-tumour cell lines. Under in vivo conditions, three application routes of phenylboronic acid were studied: intra-peritoneal (i.p.), intra-tumour (i.t.) and per-oral. After tumour transplantation in syngeneic mice, phenylboronic acid was shown to slow the growth of both tumour cell lines (4T1 and SCCVII) compared with the control. The inhibitory effects were pronounced during the application of phenylboronic acid. For both tested tumour cell lines, the most prominent antitumour effect was obtained by intraperitoneal administration, followed significantly by oral administration.
Collapse
Affiliation(s)
- Maja Marasovic
- Faculty of Chemistry and Technology, University of Split, Split, Croatia
| | - Sinisa Ivankovic
- Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
| | - Ranko Stojkovic
- Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
| | - Damir Djermic
- Division of Molecular Biology, Rudjer Boskovic Institute, Zagreb, Croatia
| | - Borivoj Galic
- Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Mladen Milos
- Faculty of Chemistry and Technology, University of Split, Split, Croatia
| |
Collapse
|
|
37
|
Wu JZ, Williams GR, Li HY, Wang DX, Li SD, Zhu LM. Insulin-loaded PLGA microspheres for glucose-responsive release. Drug Deliv 2017; 24:1513-1525. [PMID: 28975813 PMCID: PMC8241149 DOI: 10.1080/10717544.2017.1381200] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 09/11/2017] [Accepted: 09/14/2017] [Indexed: 12/16/2022] Open
Abstract
Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N-vinylcaprolactam); p(AAPBA-co-NVCL)]. Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83 ± 0.15 and 82.6 ± 5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes.
Collapse
Affiliation(s)
- Jun-Zi Wu
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, P.R. China
| | | | - He-Yu Li
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, P.R. China
| | - Dong-Xiu Wang
- Central Laboratory, Environmental Monitoring Center of Kunming, Kunming, P.R. China
| | - Shu-De Li
- School of Basic Medical Sciences, Kunming Medical University, Kunming, P.R. China
| | - Li-Min Zhu
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, P.R. China
| |
Collapse
|
|
38
|
Pérez-Rodríguez M, García-Mendoza E, Farfán-García ED, Das BC, Ciprés-Flores FJ, Trujillo-Ferrara JG, Tamay-Cach F, Soriano-Ursúa MA. Not all boronic acids with a five-membered cycle induce tremor, neuronal damage and decreased dopamine. Neurotoxicology 2017; 62:92-99. [PMID: 28595910 DOI: 10.1016/j.neuro.2017.06.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Revised: 06/02/2017] [Accepted: 06/02/2017] [Indexed: 02/07/2023]
Abstract
Several striatal toxins can be used to induce motor disruption. One example is MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), whose toxicity is accepted as a murine model of parkinsonism. Recently, 3-Thienylboronic acid (3TB) was found to produce motor disruption and biased neuronal damage to basal ganglia in mice. The aim of this study was to examine the toxic effects of four boronic acids with a close structural relationship to 3TB (all having a five-membered cycle), as well as boric acid and 3TB. These boron-containing compounds were compared to MPTP regarding brain access, morphological disruption of the CNS, and behavioral manifestations of such disruption. Data was collected through acute toxicity evaluations, motor behavior tests, necropsies, determination of neuronal survival by immunohistochemistry, Raman spectroscopic analysis of brain tissue, and HPLC measurement of dopamine in substantia nigra and striatum tissue. Each compound showed a distinct profile for motor disruption. For example, motor activity was not disrupted by boric acid, but was decreased by two boronic acids (caused by a sedative effect). 3TB, 2-Thienyl and 2-furanyl boronic acid gave rise to shaking behavior. The various manifestations generated by these compounds can be linked, in part, to different levels of dopamine (measured by HPLC) and degrees of neuronal damage in the basal ganglia and cerebellum. Clearly, motor disruption is not induced by all boronic acids with a five-membered cycle as substituent. Possible explanations are given for the diverse chemico-morphological changes and degrees of disruption of the motor system, considering the role of boron and the structure-toxicity relationship.
Collapse
Affiliation(s)
- Maribel Pérez-Rodríguez
- Departamentos de Fisiología, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - Esperanza García-Mendoza
- Departamento de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Av. Insurgentes Sur No. 3877, Col. La Fama, Del. Tlalpan, México City, Mexico
| | - Eunice D Farfán-García
- Departamentos de Fisiología, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - Bhaskar C Das
- Departments of Medicine and Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, Madison Avenue, Box 1243 New York, NY 10029, USA
| | - Fabiola J Ciprés-Flores
- Departamentos de Fisiología, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - José G Trujillo-Ferrara
- Departamentos de Fisiología, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - Feliciano Tamay-Cach
- Departamentos de Fisiología, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico
| | - Marvin A Soriano-Ursúa
- Departamentos de Fisiología, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, Mexico.
| |
Collapse
|
|
39
|
García-Ávila AK, Farfán-García ED, Guevara-Salazar JA, Trujillo-Ferrara JG, Soriano-Ursúa MA. Scope of translational medicine in developing boron-containing compounds for therapeutics. World J Transl Med 2017; 6:1-9. [DOI: 10.5528/wjtm.v6.i1.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 02/23/2017] [Accepted: 03/13/2017] [Indexed: 02/06/2023] Open
Abstract
The ubiquitousness of naturally occurring boron-containing compounds (BCCs) has led to their constant contact with humankind. Recently, many synthetic BCCs have been elaborated for a broad spectrum of purposes, especially boric, boronic and borinic acids. Although BCCs were once employed primarily as antiseptics and later as antibiotics, they have become an increasingly relevant therapeutic tool. Nevertheless, this potential of BCCs has been drastically limited due to some unfortunate intra-hospital accidents in the 1940s and 1950s. The increasing use of BCCs as insecticides, antimicrobials, and other agents is providing new insights into their role in the physiology of several living species and in the pathophysiology of humans. It is becoming clear that BCCs act through a wide range of mechanisms, as do their corresponding boron-free counterparts. When comparing BCCs and similar boron-free compounds, in many cases the former show advantages in the medical field. The current mini-review focuses on how BCCs have been developed by means of translational medicine, a process connecting biomedical research with clinical applications. This process of discovery is currently in an exponential stage.
Collapse
|
|
40
|
Farfán-García ED, Pérez-Rodríguez M, Espinosa-García C, Castillo-Mendieta NT, Maldonado-Castro M, Querejeta E, Trujillo-Ferrara JG, Soriano-Ursúa MA. Disruption of motor behavior and injury to the CNS induced by 3-thienylboronic acid in mice. Toxicol Appl Pharmacol 2016; 307:130-137. [PMID: 27495897 DOI: 10.1016/j.taap.2016.08.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Revised: 07/30/2016] [Accepted: 08/01/2016] [Indexed: 02/07/2023]
Abstract
The scarcity of studies on boron containing compounds (BCC) in the medicinal field is gradually being remedied. Efforts have been made to explore the effects of BCCs due to the properties that boron confers to molecules. Research has shown that the safety of some BCCs is similar to that found for boron-free compounds (judging from the acute toxicological evaluation). However, it has been observed that the administration of 3-thienylboronic acid (3TB) induced motor disruption in CD1 mice. In the current contribution we studied in deeper form the disruption of motor performance produced by the intraperitoneal administration of 3TB in mice from two strains (CD1 and C57BL6). Disruption of motor activity was dependent not only on the dose of 3TB administered, but also on the DMSO concentration in the vehicle. The ability of 3TB to enter the Central Nervous System (CNS) was evidenced by Raman spectroscopy as well as morphological effects on the CNS, such as loss of neurons yielding biased injury to the substantia nigra and striatum at doses ≥200mg/kg, and involving granular cell damage at doses of 400mg/kg but less injury in the motor cortex. Our work acquaints about the use of this compound in drug design, but the interesting profile as neurotoxic agent invite us to study it regarding the damage on the motor system.
Collapse
Affiliation(s)
- E D Farfán-García
- Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México, Mexico
| | - M Pérez-Rodríguez
- Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México, Mexico
| | - C Espinosa-García
- Departamento de Biología de la Reproducción, Universidad Autónoma Metropolitana (UAM), 09310 Ciudad de México, Mexico
| | - N T Castillo-Mendieta
- Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México, Mexico
| | - M Maldonado-Castro
- Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México, Mexico
| | - E Querejeta
- Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México, Mexico
| | - J G Trujillo-Ferrara
- Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México, Mexico
| | - M A Soriano-Ursúa
- Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México, Mexico.
| |
Collapse
|
|
41
|
Farfán-García ED, Castillo-Mendieta NT, Ciprés-Flores FJ, Padilla-Martínez II, Trujillo-Ferrara JG, Soriano-Ursúa MA. Current data regarding the structure-toxicity relationship of boron-containing compounds. Toxicol Lett 2016; 258:115-125. [PMID: 27329537 DOI: 10.1016/j.toxlet.2016.06.018] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 05/29/2016] [Accepted: 06/17/2016] [Indexed: 02/07/2023]
Abstract
Boron is ubiquitous in nature, being an essential element of diverse cells. As a result, humans have had contact with boron containing compounds (BCCs) for a long time. During the 20th century, BCCs were developed as antiseptics, antibiotics, cosmetics and insecticides. Boric acid was freely used in the nosocomial environment as an antiseptic and sedative salt, leading to the death of patients and an important discovery about its critical toxicology for humans. Since then the many toxicological studies done in relation to BCCs have helped to establish the proper limits of their use. During the last 15 years, there has been a boom of research on the design and use of new, potent and efficient boron containing drugs, finding that the addition of boron to some known drugs increases their affinity and selectivity. This mini-review summarizes two aspects of BCCs: toxicological data found with experimental models, and the scarce but increasing data about the structure-activity relationship for toxicity and therapeutic use. As is the case with boron-free compounds, the biological activity of BCCs is related to their chemical structure. We discuss the use of new technology to discover potent and efficient BCCs for medicinal therapy by avoiding toxic effects.
Collapse
Affiliation(s)
- E D Farfán-García
- Departamento de Bioquímica, Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, 11340, México City, México; Departamento de Fisiología, Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, 11340, México City, México
| | - N T Castillo-Mendieta
- Departamento de Fisiología, Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, 11340, México City, México
| | - F J Ciprés-Flores
- Departamento de Bioquímica, Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, 11340, México City, México; Departamento de Fisiología, Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, 11340, México City, México
| | - I I Padilla-Martínez
- Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Avenida Acueducto s/n, Barrio La Laguna Ticomán, 07340, México
| | - J G Trujillo-Ferrara
- Departamento de Bioquímica, Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, 11340, México City, México
| | - M A Soriano-Ursúa
- Departamento de Fisiología, Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, 11340, México City, México.
| |
Collapse
|
|
42
|
Tang J, Zheng XT, Xiao K, Wang KL, Wang J, Wang YX, Wang K, Wang W, Lu S, Yang KL, Sun PP, Khaliq H, Zhong J, Peng KM. Effect of Boric Acid Supplementation on the Expression of BDNF in African Ostrich Chick Brain. Biol Trace Elem Res 2016; 170:208-15. [PMID: 26226831 DOI: 10.1007/s12011-015-0428-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Accepted: 06/26/2015] [Indexed: 02/07/2023]
Abstract
The degree of brain development can be expressed by the levels of brain brain-derived neurotrophic factor (BDNF). BDNF plays an irreplaceable role in the process of neuronal development, protection, and restoration. The aim of the present study was to evaluate the effects of boric acid supplementation in water on the ostrich chick neuronal development. One-day-old healthy animals were supplemented with boron in drinking water at various concentrations, and the potential effects of boric acid on brain development were tested by a series of experiments. The histological changes in brain were observed by hematoxylin and eosin (HE) staining and Nissl staining. Expression of BDNF was analyzed by immunohistochemistry, quantitative real-time PCR (QRT-PCR), and enzyme linked immunosorbent assay (ELISA). Apoptosis was evaluated with Dutp-biotin nick end labeling (TUNEL) reaction, and caspase-3 was detected with QRT-PCR. The results were as follows: (1) under the light microscope, the neuron structure was well developed with abundance of neurites and intact cell morphology when animals were fed with less than 160 mg/L of boric acid (groups II, III, IV). Adversely, when boric acid doses were higher than 320 mg/L(groups V, VI), the high-dose boric acid neuron structure was damaged with less neurites, particularly at 640 mg/L; (2) the quantity of BDNF expression in groups II, III, and IV was increased while it was decreased in groups V and VI when compared with that in group I; (3) TUNEL reaction and the caspase-3 mRNA level showed that the amount of cell apoptosis in group II, group III, and group IV were decreased, but increased in group V and group VI significantly. These results indicated that appropriate supplementation of boric acid, especially at 160 mg/L, could promote ostrich chicks' brain development by promoting the BDNF expression and reducing cell apoptosis. Conversely, high dose of boric acid particularly in 640 mg/L would damage the neuron structure of ostrich chick brain by inhibiting the BDNF expression and increasing cell apoptosis. Taken together, the 160 mg/L boric acid supplementation may be the optimal dose for the brain development of ostrich chicks.
Collapse
Affiliation(s)
- Juan Tang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
- Huangshi Center for Animal Disease Control and Prevention, Huangshi Bureau of Animal Husbandry and Veterinary, Huangshi, 435000, HuBei, China.
| | - Xing-ting Zheng
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Ke Xiao
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Kun-lun Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Jing Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Yun-xiao Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Ke Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Wei Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Shun Lu
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Ke-li Yang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Peng-Peng Sun
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Haseeb Khaliq
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Juming Zhong
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
- College of Veterinary Medicine, Auburn University, Auburn, AL, USA
| | - Ke-Mei Peng
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
| |
Collapse
|
|
43
|
Nistor PA, May PW, Tamagnini F, Randall AD, Caldwell MA. Long-term culture of pluripotent stem-cell-derived human neurons on diamond – A substrate for neurodegeneration research and therapy. Biomaterials 2015; 61:139-49. [PMID: 26002787 DOI: 10.1016/j.biomaterials.2015.04.050] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Revised: 04/24/2015] [Accepted: 04/30/2015] [Indexed: 12/11/2022]
|
|
44
|
Soriano-Ursúa MA, Arias-Montaño JA, Correa-Basurto J, Hernández-Martínez CF, López-Cabrera Y, Castillo-Hernández MC, Padilla-Martínez II, Trujillo-Ferrara JG. Insights on the role of boron containing moieties in the design of new potent and efficient agonists targeting the β2 adrenoceptor. Bioorg Med Chem Lett 2015; 25:820-825. [PMID: 25592716 DOI: 10.1016/j.bmcl.2014.12.077] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Revised: 12/20/2014] [Accepted: 12/23/2014] [Indexed: 02/07/2023]
Abstract
The development of β2 adrenoceptor (β2AR) agonists is of increasing interest because of their wide-ranging applications in medicine, particularly for the treatment of pulmonary diseases. Regarding the relaxation of smooth muscle that lines airways of mammals, some boron-containing adducts have demonstrated greater potency and efficacy compared to well-known boron-free compounds. We herein report the design and synthesis as well as the chemical and pharmacological characterization of a new boron-containing compound: ((R)-6-((S)-2-(tert-butylammonio)-1-hydroxyethyl)-2-hydroxy-2-isobutyl-4H-benzo[d][1,3,2] dioxaborinin-2-uide). Compared to its precursor (salbutamol), this compound induced relaxation of smooth muscle in guinea pig tracheal rings with greater potency and efficacy (EC50⩽28.02nM). Theoretical studies suggest the potential selectivity of this boron containing compound on the orthosteric site of beta adrenoceptors and/or signaling pathways, as well as the importance of the tetracoordinated boron atom in its structure for binding recognition properties.
Collapse
Affiliation(s)
- Marvin A Soriano-Ursúa
- Departamentos de Fisiología y Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, México, D.F. C.P. 11340, Mexico; Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico.
| | - José A Arias-Montaño
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del I.P.N., Av. IPN 2508, 07360 Mexico, D.F., Mexico
| | - José Correa-Basurto
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico
| | - Christian F Hernández-Martínez
- Departamentos de Fisiología y Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, México, D.F. C.P. 11340, Mexico
| | - Yessica López-Cabrera
- Departamentos de Fisiología y Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, México, D.F. C.P. 11340, Mexico
| | - Maria C Castillo-Hernández
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico
| | - Itzia I Padilla-Martínez
- Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Avenida Acueducto s/n, Barrio La Laguna Ticomán, 07340, Mexico
| | - José G Trujillo-Ferrara
- Departamentos de Fisiología y Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, México, D.F. C.P. 11340, Mexico
| |
Collapse
|
|
45
|
Hernández-Paredes J, Olvera-Tapia AL, Arenas-García JI, Höpfl H, Morales-Rojas H, Herrera-Ruiz D, Gonzaga-Morales AI, Rodríguez-Fragoso L. On molecular complexes derived from amino acids and nicotinamides in combination with boronic acids. CrystEngComm 2015; 17:5166-5186. [DOI: 10.1039/c4ce01934b] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
46
|
Scott H, Walmsley RM. Ames positive boronic acids are not all eukaryotic genotoxins. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2014; 777:68-72. [PMID: 25726177 DOI: 10.1016/j.mrgentox.2014.12.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Revised: 12/04/2014] [Accepted: 12/05/2014] [Indexed: 12/20/2022]
Abstract
Boronic acids and their derivatives have been exploited for their pharmacological activity and their utility as intermediates in the synthesis of novel non-boron containing compounds. A recent study reported that boronic acids are bacterial mutagens. Here, results are reported from the testing of nine boronic acids using the pan-mechanistic eukaryotic GADD45a genotoxicity assays, BlueScreen HC and GreenScreen HC. Positive results were produced for one compound in GreenScreen and four compounds in BlueScreen. Only negative results were produced when tested with S9 metabolic activation. These data suggest that there is not a general genotoxic liability in eukaryotes, within this chemical domain. Furthermore, they are not potent eukaryotic genotoxins: positive results were produced only at concentrations between 1mM and 10mM. Their presence as low concentration contaminants or impurities would be unlikely to produce misleading positive results for a test material.
Collapse
Affiliation(s)
- Heather Scott
- Gentronix Ltd., BioHub at Alderley Park, Cheshire, SK10 4TG, United Kingdom
| | - Richard M Walmsley
- Gentronix Ltd., BioHub at Alderley Park, Cheshire, SK10 4TG, United Kingdom; Faculty of Life Sciences, University of Manchester, M13 9PL, United Kingdom.
| |
Collapse
|
|
47
|
Liu CT, Tomsho JW, Benkovic SJ. The unique chemistry of benzoxaboroles: current and emerging applications in biotechnology and therapeutic treatments. Bioorg Med Chem 2014; 22:4462-73. [PMID: 24864040 DOI: 10.1016/j.bmc.2014.04.065] [Citation(s) in RCA: 96] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Revised: 04/21/2014] [Accepted: 04/30/2014] [Indexed: 12/25/2022]
Abstract
Benzoxaboroles have garnered much attention in recent years due to their diverse applications in bio-sensing technology, material science, and therapeutic intervention. Part of the reason arises from the benzoxaboroles' unique chemical properties, especially in comparison to their acyclic boronic acid counterparts. Furthermore, the low bio-toxicity combined with the high target specificity associated with benzoxaboroles make them very attractive as therapeutic agents. Herein, we provide an updated summary on the current knowledge of the fundamental chemical reactivity of benzoxaboroles, followed by highlighting their major applications reported to date.
Collapse
Affiliation(s)
- C Tony Liu
- Department of Chemistry, Pennsylvania State University, University Park, PA 16802, United States
| | - John W Tomsho
- Department of Chemistry & Biochemistry, University of the Sciences, 600 S. 43rd Street, Philadelphia, PA 19104-4495, United States.
| | - Stephen J Benkovic
- Department of Chemistry, Pennsylvania State University, University Park, PA 16802, United States.
| |
Collapse
|
|
48
|
Soriano-Ursúa MA, Das BC, Trujillo-Ferrara JG. Boron-containing compounds: chemico-biological properties and expanding medicinal potential in prevention, diagnosis and therapy. Expert Opin Ther Pat 2014; 24:485-500. [PMID: 24456081 DOI: 10.1517/13543776.2014.881472] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Although the medicinal use of boron-containing compounds (BCCs) had long been limited to antiseptics, in the last few decades, these compounds have been used as antibiotics or chemotherapeutic agents. In the last few years, boron has been included in the moieties of many known drugs to improve their capacity in binding to their respective target receptors. AREAS COVERED The current review focuses on research and patent literature of the last decade related to the development of BCCs as preventive, diagnostic and therapeutic tools. It explores the possible mechanisms of action of these compounds as well as the advantageous features of their structure and chemico-pharmacological properties. EXPERT OPINION Although uncertainties exist about the mechanism of action of BCCs, increasing evidence about their toxicological profile strongly suggests that many can be safely administered to humans. Even stronger evidence exists regarding the capacity of BCCs to reach multiple targets that are involved in the treatment of common diseases. It seems fair to say that some BCCs will reach the market for medicinal use in the near future, not only for targeting microbial or neoplastic systems but also for acting on cell-signaling processes involved in many other disorders.
Collapse
Affiliation(s)
- Marvin A Soriano-Ursúa
- Departamento de Fisiología and Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional , Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Del. Miguel Hidalgo, México City, D.F, 11340 , México +52 555 7296000 ; +52 555 7296000-Ext 62751 ;
| | | | | |
Collapse
|
|
49
|
Reix N, Moreau F, Spizzo AH, Canel C, Catargi B, Sigrist S, Jeandidier N. Les insulines intelligentes : une nouvelle forme de pancréas artificiel. MÉDECINE DES MALADIES MÉTABOLIQUES 2014; 8:141-146. [DOI: 10.1016/s1957-2557(14)70726-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|